Synthetic efforts toward the natural products (-)-verrucarol and psiguadial A & aniline N-oxide functionalization
Date
2017
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
University of Delaware
Abstract
The first project involves our efforts toward the core structure of the
macrocyclic trichothecene (–)-verrucarol (3). We developed a short synthetic concept
for the enantioselective synthesis of the natural product. The key step is an
asymmetric intramolecular Mizoroki-Heck reaction. In order to evaluate the key step,
we synthesized several substrates and screened various reaction conditions. ☐ The second project involves the discovery of a method for the functionalization
of aniline-N-oxides. Discovery of the method took place while searching for a general
method for the generation of aza-ortho-xylylenes in situ. We found the reaction to be
quite general, allowing us to access aminophenols, aminoarylsulfonates, alkylated
anilines, and aminoanilines in 29−95% yield in a single laboratory operation from
easily isolable, bench-stable N,N-dialkylaniline N-oxides. ☐ The final project involves our efforts toward the total synthesis of the
meroterpenoid psiguadial A (190). The key step is an enolate–ortho-quinone methide
(o-QM) reaction followed by an oxa-Michael addition to form the seven-member
heterocyclic ring. The first generation synthesis toward the terpene derived silyl enol
ether (225) was investigated. In an effort to better understand and optimize the two
key steps in the synthesis, a model system of psiguadial A (190) was developed. We
successfully synthesized the product of the enolate–o-QM reaction, that is, the keto
phenol (254A). Evaluation of the oxa-Michael reaction, did not return the desired
products. Several synthetic strategies were developed and implemented, but did not
lead to the seven-member heterocyclic ring. Current efforts involve the synthesis of
intermediates of form the seven-member heterocycle to form the via copper-catalyzed
C-O coupling. A second generation of the silyl enol ether (225) is also being
investigated and addresses the major problems of the first generation’s synthetic
challenges.
Description
Keywords
Pure sciences, (–)-Verrucarol, Aniline N-oxide functionalization, Natural products, Psiguadial A, Synthetic efforts